(a) Field of the Invention
The present invention relates to a poly(organophosphazene)-superparamagnetic nanoparticle complex including a thermosensitive/biodegradable poly(organophosphazene) and a iron oxide (Fe3O4, Magnetite)-series ferrite superparamagnetic nanoparticle, a preparation method, and uses of carrying a physiologically-active material, biomaterial and a MRI contrast agent. The above phosphazene polymer has reversible sol-to-gel phase transition, biodegradability, and thermosensitivity, and includes a chemical bond formed by at least one method selected from UV radiation, cross-linking agent treatment, additive treatment, enzyme treatment and the addition of at least a polymer.
(b) Description of the Related Art
The phase of thermosensitive hydrogel is sol at low temperature and turns into gel as the temperature increases. The sol-to-gel phase transition can be observed reversibly. Because the thermosensitive hydrogel is in an aqueous polymer solution at room temperature, it can be easily mixed with a therapeutic drug. In addition, if the thermosensitive hydrogel is injected into a needed region without surgical treatment, it forms a three dimensional structure with the body heat and thus is capable of releasing a drug slowly. Thus, the thermosensitive hydrogel has been evaluated highly as an injectable carrier material for drug delivery.
When the thermosensitive hydrogel is used as injectable carrier material, a drug with a low weight-average molecular weight or high hydrophilicity is injected into a body with the polymer carrier, and can be released easily through the three dimensional network structure of gel. 30% or more of the loaded drugs are released at the early stage and the release of drug completes in a short time due to the high diffusion rate of hydrophilic drug (Adv. Drug Deliv. Rev., 31, 197 (1998)).
To remedy the problem, the thermosensitive hydrogel of which a functional group is able to conjugate directly with a drug was introduced. When the thermosensitive polymer conjugated chemically with a hydrophilic drug is injected into a body, the drug can be sustainedly released by degrading tendency of the polymer or the chemical bond between the polymer and drug. The sustained release of drug and the degradation of thermosensitive hydrogel were proven by in vitro experiment. In in vivo experiment, however, there has not been noninvasive method to monitor the behavior of polymer within a body including the degrading tendency of the polymer injected into a body.
The present inventors substituted the dichlorophosphazene linear polymer with amino acid ester and methoxypolyethylene glycol, found that the substituted phosphazene polymer showed a sol-to-gel phase transition where the polymer was in an aqueous solution under the certain temperature but turned into a three-dimensional structural gel above a certain temperature, and reported that the thermosensitive phosphazene polymer was hydrolyzed slowly in an aqueous solution (Macromolecules 32, 2188 (1999), Macromolecules 32, 7820 (1999), Macromolecules 35, 3876 (2002), KR patent no. 10-0259367, KR patent no. 10-0315630, and U.S. Pat. No. 6,319,984).